Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study / Axel KRUG in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) . - 54 p. Titre : Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study Type de document : texte imprimé Auteurs : Axel KRUG, Auteur ; Markus WÖHR, Auteur ; Dominik SEFFER, Auteur ; Henrike RIPPBERGER, Auteur ; A. Özge SUNGUR, Auteur ; Bruno DIETSCHE, Auteur ; Frederike STEIN, Auteur ; Sugirthan SIVALINGAM, Auteur ; Andreas J. FORSTNER, Auteur ; Stephanie H. WITT, Auteur ; Helene DUKAL, Auteur ; Fabian STREIT, Auteur ; Anna MAASER, Auteur ; Stefanie HEILMANN-HEIMBACH, Auteur ; Till F.M. ANDLAUER, Auteur ; Stefan HERMS, Auteur ; Per HOFFMANN, Auteur ; Marcella RIETSCHEL, Auteur ; Markus M. NÖTHEN, Auteur ; Martin LACKINGER, Auteur ; Gerhard SCHRATT, Auteur ; Michael KOCH, Auteur ; Rainer K.W. SCHWARTING, Auteur ; Tilo KIRCHER, Auteur Article en page(s) : 54 p. Langues : Anglais (eng) Mots-clés : Advanced paternal age (APA)  Diffusion tension imaging (DTI)  Social behavior  Ultrasonic vocalization  Voxel-based morphometry (VBM) Index. décimale : PER Périodiques Résumé : Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N = 677). Paternal age was further positively associated with gray matter volume (VBM, N = 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI, N = 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction. En ligne : http://dx.doi.org/10.1186/s13229-020-00345-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 [article] Advanced paternal age as a risk factor for neurodevelopmental disorders: a translational study [texte imprimé] / Axel KRUG, Auteur ; Markus WÖHR, Auteur ; Dominik SEFFER, Auteur ; Henrike RIPPBERGER, Auteur ; A. Özge SUNGUR, Auteur ; Bruno DIETSCHE, Auteur ; Frederike STEIN, Auteur ; Sugirthan SIVALINGAM, Auteur ; Andreas J. FORSTNER, Auteur ; Stephanie H. WITT, Auteur ; Helene DUKAL, Auteur ; Fabian STREIT, Auteur ; Anna MAASER, Auteur ; Stefanie HEILMANN-HEIMBACH, Auteur ; Till F.M. ANDLAUER, Auteur ; Stefan HERMS, Auteur ; Per HOFFMANN, Auteur ; Marcella RIETSCHEL, Auteur ; Markus M. NÖTHEN, Auteur ; Martin LACKINGER, Auteur ; Gerhard SCHRATT, Auteur ; Michael KOCH, Auteur ; Rainer K.W. SCHWARTING, Auteur ; Tilo KIRCHER, Auteur . - 54 p. Langues : Anglais (eng) in Molecular Autism > 11 (2020) . - 54 p. Mots-clés : Advanced paternal age (APA)  Diffusion tension imaging (DTI)  Social behavior  Ultrasonic vocalization  Voxel-based morphometry (VBM) Index. décimale : PER Périodiques Résumé : Advanced paternal age (APA) is a risk factor for several neurodevelopmental disorders, including autism and schizophrenia. The potential mechanisms conferring this risk are poorly understood. Here, we show that the personality traits schizotypy and neuroticism correlated with paternal age in healthy subjects (N = 677). Paternal age was further positively associated with gray matter volume (VBM, N = 342) in the right prefrontal and the right medial temporal cortex. The integrity of fiber tracts (DTI, N = 222) connecting these two areas correlated positively with paternal age. Genome-wide methylation analysis in humans showed differential methylation in APA individuals, linking APA to epigenetic mechanisms. A corresponding phenotype was obtained in our rat model. APA rats displayed social-communication deficits and emitted fewer pro-social ultrasonic vocalizations compared to controls. They further showed repetitive and stereotyped patterns of behavior, together with higher anxiety during early development. At the neurobiological level, microRNAs miR-132 and miR-134 were both differentially regulated in rats and humans depending on APA. This study demonstrates associations between APA and social behaviors across species. They might be driven by changes in the expression of microRNAs and/or epigenetic changes regulating neuronal plasticity, leading to brain morphological changes and fronto-hippocampal connectivity, a network which has been implicated in social interaction. En ligne : http://dx.doi.org/10.1186/s13229-020-00345-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427

Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context / A. Özge SUNGUR in Autism Research, 9-6 (June 2016)  

Public ISBD [article]  inAutism Research > 9-6 (June 2016) . - p.696-709 Titre : Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context Type de document : texte imprimé Auteurs : A. Özge SUNGUR, Auteur ; Rainer K.W. SCHWARTING, Auteur ; Markus WÖHR, Auteur Article en page(s) : p.696-709 Langues : Anglais (eng) Mots-clés : animal model  postsynaptic density  neurodevelopmental disorders  autism  communication  ultrasonic vocalization  social context Index. décimale : PER Périodiques Résumé : Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation-induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1−/− null mutant, Shank1+/− heterozygous, and Shank1+/+ wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD-related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1−/− pups vocalized less and displayed a delay in the typical inverted U-shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype-dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696–709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1564 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=290 [article] Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context [texte imprimé] / A. Özge SUNGUR, Auteur ; Rainer K.W. SCHWARTING, Auteur ; Markus WÖHR, Auteur . - p.696-709. Langues : Anglais (eng) in Autism Research > 9-6 (June 2016) . - p.696-709 Mots-clés : animal model  postsynaptic density  neurodevelopmental disorders  autism  communication  ultrasonic vocalization  social context Index. décimale : PER Périodiques Résumé : Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation-induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1−/− null mutant, Shank1+/− heterozygous, and Shank1+/+ wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD-related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1−/− pups vocalized less and displayed a delay in the typical inverted U-shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype-dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696–709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1564 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=290

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